every 3 months, and 2 mg i.v. every 2 months) were compared to ACE doses ≤7.2 mg (100 mg oral monthly, 50/50 mg monthly, and 2.5 mg oral daily) and to low 5.5 mg ACE dose (oral

2.5 mg daily). A dose–response effect on ON-01910 solubility dmso nonvertebral fractures was observed when comparing high with low ACE doses. The comparison resulted in a 0.62 RR (95% CI, 0.396–0.974; p = 0.038) for ACE doses ≥10.8 mg learn more vs. to 5.5 mg ACE doses and in a 0.64 RR (95% CI, 0.43–0.94) for ≥10.8 mg ACE doses vs. ≤7.2 mg ACE doses, leading to the conclusion that higher ibandronate dose levels (150 mg monthly or 3 mg i.v. quarterly) significantly reduced nonvertebral fracture risk in postmenopausal women. In a similar analysis, Harris et al. compared reduction in fracture risk for high (≥10.8 mg), mid (7.2–5.5 mg), and low (≤4.0 mg) ACE relative to placebo [74]. It was observed that doses of ibandronate resulting in ACEs ≥10.8 mg, including the marketed oral 150 mg monthly and i.v. 3 mg thrice monthly, significantly reduce the risk of all clinical, vertebral, and nonvertebral fractures with a 0.712 RR (95% CI, 0.55–0.92; p = 0.01). The risk of nonvertebral fractures was also significantly reduced with a 0.701 RR (95% CI, 0.50–0.99; p = 0.04). Data from the four phase III clinical trials of ibandronate (8,710 patients) were pooled in a meta-analysis to assess the relationship between ibandronate dose, BMD changes, and rates of both clinical and

nonvertebral fractures [75]. It was observed that both lumbar spine and total hip BMD increased with increasing ibandronate dose. A statistically significant inverse linear BMS202 price (-)-p-Bromotetramisole Oxalate relationship has been reported between percent change in lumbar spine BMD and the rate of clinical fractures (p = 0.005). There is no evidence, from placebo-controlled trials, for a reduction of nonvertebral fracture with ibandronate,

but data from the MOBILE bridging study, from meta-analysis and from ACE evaluations, suggest a significant effect of the marketed oral 150 and the 3 mg i.v. ibandronate on the risk reduction of nonvertebral fractures. Hip, nonvertebral, or clinical fracture rates were not statistically different between patients receiving monthly oral ibandronate, weekly oral alendronate, or risedronate in a 12-month observational study, but patients on oral ibandronate had a significantly 64% lower risk of vertebral fractures than patients on weekly bisphosphonates (RR, 0.36; 95% CI, 0.18–0.75; p = 0.006) [76]. Both oral 2.5 mg daily and intermittent oral ibandronate dosage (20 mg every other day for 12 doses every 3 months) were well tolerated with an incidence of adverse events similar to placebo in the BONE trial [69]. Once-monthly oral ibandronate was well tolerated, with a similar safety profile to placebo in a 3-month, double-blind, placebo-controlled, phase I study (Monthly Oral Pilot Study) [77] and with a similar incidence of adverse events across groups (oral 50 + 50, 100, and 150 mg) in the MOBILE study [70].